It is widely acknowledged that psychoactive drugs, including tetrahydrocannabinol (THC), the major psychoactive agent in marijuana, have a detrimental effect on immunity. Studies on this subject have been somewhat limited since most have been done with adults or lymphoid cells from such adults. In order to overcome this deficit, the proposed project is concerned with the study of lymphoid cells from the thymus, spleen and lymph nodes of very young in comparison to adult and then to very old mice in terms of the effect of THC on lymphocyte function. In this regard, it is well documented that the immune responses of the very young and very old are depressed as compared to adults. This depression involves mainly T cell function. The parameters to be measured include mitogen induced proliferation, interleukin production, and cytotoxic, helper and suppressor activity of untreated lymphoid cells as compared to THC-treated cells in vitro. The cells effected will be monitored by fluorescent activated cell sorter (FACS) analysis to determine which cell types are affected by THC. Lymphoid cells will be separated into T cell enriched populations and then onto helper vs suppressor/effector cell subpopulations to elucidate the effects of THC on these subpopulations. In addition, the effects of THC on suboptimal immune systems (very young and very old mice) will be examined. In this regard, the age range of individuals using marijuana has been decreasing, and marijuana has been given therapeutically to already immunosuppressed individuals (i.e., cancer patients). In addition, individuals with chronic immunosuppressing infections (including AIDS) are often marijuana users. Preliminary results in this laboratory extent of suppression to THC and the young age of mice as well as increased susceptibility of thymocytes (immature) lymphoid cells vs spleen and lymph node cells (i.e., mature) in regard to THC immunosuppression. The proposed studies will provide important information concerning suppressive effects of THC on cellular immunity. The age comparative studies will provide information directly applicable to individuals of extreme ages using this drug as well as elucidating the effects of THC on individuals with suboptimal immunity.